NCT00892177|CompletedPhase 2ResultsDMC

Dasatinib and Bevacizumab in Treating Patients With Recurrent or Progressive High-Grade Glioma or Glioblastoma Multiforme

Phase I/Randomized Phase II Double Blind Study of Either Dasatinib or Placebo Combined With Bevacizumab in Recurrent Glioblastoma

Alliance for Clinical Trials in Oncology ClinicalTrials.gov

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3 other identifiers

NCCTG-N0872NCI-2011-01921CDR0000641746

Study Type

interventional

Target

144

Locations

1 country

Sites

305

Timeline

RegisteredMay 2009

StartedOct 2009

CompletionJul 2019

Brief Summary

RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also block the growth of the tumor by blocking blood flow to the tumor. It is not yet known whether bevacizumab together with dasatinib are more effective than a placebo in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme. PURPOSE: This randomized phase I/II trial (Phase I completed) is studying the side effects and best dose of dasatinib when given together with bevacizumab and to see how well it works compared to placebo in treating patients with recurrent or progressive high-grade glioma or glioblastoma multiforme.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

144

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Oct 2009

Longer than P75 for phase_2

Geographic Reach

1 country

305 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.8 years study duration

First Submitted

Initial submission to the registry

May 1, 2009

Completed

3 days until next milestone

First Posted

Study publicly available on registry

May 4, 2009

Completed

5 months until next milestone

Study Start

First participant enrolled

October 1, 2009

Completed

5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2014

Completed

2.7 years until next milestone

Results Posted

Study results publicly available

June 27, 2017

Completed

2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2019

Completed

Last Updated

October 21, 2019

Status Verified

October 1, 2019

Enrollment Period

5.1 years

First QC Date

May 1, 2009

Results QC Date

March 13, 2017

Last Update Submit

October 4, 2019

Conditions

Glioblastoma Multiforme

Keywords

adult giant cell glioblastomaadult glioblastomaadult gliosarcomaadult mixed gliomarecurrent adult brain tumoradult anaplastic oligodendrogliomaadult oligodendrogliomaadult anaplastic astrocytoma

Outcome Measures

Primary Outcomes (2)

Number of Participants With Dose Limiting Toxicities to Determine Maximum Tolerated Dose (MTD) of Dasatinib in Combination With Bevacizumab (Phase I)
The Maximum Tolerated Dose (MTD) will be based on the assessment of dose-limiting toxicities (DLT) during the first 4 weeks of treatment only (i.e., following the first 2 treatment cycles), and will be defined as the dose at which fewer than one-third of patients experience a DLT to study treatment. The MTD is the dose level at which 0/6 or 1/6 patients experience DLT with the next higher dose having at least 2 out of 3 or 2 out of 6 patients encountering DLT.\> Three patients will be treated at each dose level, and can be enrolled simultaneously. If one DLT is encountered, an additional 3 patients will be added to that dose level. If at any point two DLTs are encountered within a given dose level, then the MTD has been exceeded and if only three patients have been treated at the next lower dose three more patients are treated at the next lower dose. The number of patients who developed DLTs are reported here by dose level, with the MTD reported in the statistical analysis section.
14 days
Progression-free Survival at 6 Months (PFS6) (Phase II)
The primary endpoint is the proportion of patients alive and progression-free 6 months after study treatment initiation (PFS6). All eligible consented patients that received treatment will be considered evaluable. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. PFS6 is defined as the time from start of study therapy to the date of first observation of disease progression or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The PFS6 will be estimated as the number of evaluable patients progression free and still alive at 6 months divided by the total number of evaluable patients. The confidence interval will be calculated according to the Clopper-Pearson Method.
6 months

Secondary Outcomes (5)

Number of Participants With Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 (Phase II)
Up to 3 years
Overall Survival (Phase II)
Up to 3 years
Time-to-disease Progression (Phase II)
Up to 3 years
Patient-reported QOL, as Measure by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) (Phase II)
Baseline to cycle 10 (20 weeks).
Objective Response (Phase II)
Up to 3 years

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive bevacizumab on Day 1 and dasatinib on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumabDrug: dasatinib

Arm II

ACTIVE COMPARATOR

Patients receive bevacizumab on Day 1 and placebo on days 1-14. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Biological: bevacizumabOther: placebo

Interventions

bevacizumabBIOLOGICAL

Given intravenously

Arm IArm II

dasatinibDRUG

Given orally

Arm I

placeboOTHER

Given orally

Arm II

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

≥18 years of age
Study 1: Histologic confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review.
Study 2: Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review. NOTE: Variant gliosarcomas are eligible
Evidence of tumor progression by MRI or CT scan following RT or following the most recent anti-tumor therapy. Patients who had surgical treatment at recurrence are eligible if there is imaging evidence of disease progression as compared to the first postoperative scan.
Bidimensionally measurable or evaluable disease by MRI or CT scan.
ECOG Performance Status (PS) 0, 1, or 2.
Patient willing to discontinue use of aspirin or medications that inhibit platelet function ≥ 1 week prior to registration.
Previous RT and ≥12 weeks since the completion of RT prior to registration.
The following laboratory values obtained ≤ 21 days prior to registration.
ANC ≥1500
PLT ≥100,000
Hgb \>9.0 g/dL
T. bili ≤1.5 x ULN
SGOT (AST) ≤ 3 x ULN
Creatinine ≤ ULN
+7 more criteria

You may not qualify if:

Pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception during this study and for up to 6 months after bevacizumab treatment has ended. NOTE: bevacizumab and dasatinib are investigational agents whose genotoxic effects on the developing fetus and newborn are unknown.
Prior intratumoral therapy, stereotactic radiosurgery, or interstitial brachytherapy.
EXCEPTION: Separate lesion on MRI which is not part of the previous treatment field, or convincing evidence of recurrent disease, based on biopsy, MRI spectroscopy, or PET scan.
Prior treatment with bevacizumab or VEGF-Trap (Aflibercept).
Inadequately controlled hypertension (systolic blood pressure of \>150 mmHg or diastolic pressure \>100 mmHg on anti-hypertensive medications).
NOTE: Patients with well-controlled hypertension are eligible.
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
Immunocompromised patients (other than that related to the use of corticosteroids). NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this study.
Any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or prior surgical procedures affecting absorption) that impairs ability to swallow pills.
Receiving therapeutic anticoagulation with Warfarin. NOTE: Prophylactic anticoagulation (i.e., low dose warfarin) of venous or arterial access devices is allowed, provided that INR \<1.5. Therapeutic anti-coagulation with low molecular weight heparin is allowed at time of registration.
Evidence of bleeding diathesis (greater than normal risk of bleeding) or coagulopathy (in the absence of therapeutic anticoagulation).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
Other active malignancy ≤3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma in-situ of the cervix. Note: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer.
History of myocardial infarction or unstable angina ≤6 months prior to registration.
+31 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Alliance for Clinical Trials in Oncologylead
National Cancer Institute (NCI)collaborator

Study Sites (305)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Rebecca and John Moores UCSD Cancer Center

La Jolla, California, 92093-0658, United States

Location

Palchak David MD

Pismo Beach, California, 93449, United States

Location

Aurora Presbyterian Hospital

Aurora, Colorado, 80012, United States

Location

Boulder Community Hospital

Boulder, Colorado, 80301-9019, United States

Location

Boulder Community Hospital

Boulder, Colorado, 80301, United States

Location

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, 80933, United States

Location

St. Anthony Central Hospital

Denver, Colorado, 80204, United States

Location

Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

Presbyterian - St. Luke's Medical Center

Denver, Colorado, 80218, United States

Location

St. Joseph Hospital

Denver, Colorado, 80218, United States

Location

Rose Medical Center

Denver, Colorado, 80220, United States

Location

Swedish Medical Center

Englewood, Colorado, 80110, United States

Location

North Colorado Medical Center

Greeley, Colorado, 80631, United States

Location

Sky Ridge Medical Center

Lone Tree, Colorado, 80124, United States

Location

Hope Cancer Care Center at Longmont United Hospital

Longmont, Colorado, 80501, United States

Location

McKee Medical Center

Loveland, Colorado, 80539, United States

Location

St. Mary - Corwin Regional Medical Center

Pueblo, Colorado, 81004, United States

Location

Exempla Lutheran Medical Center

Wheat Ridge, Colorado, 80033, United States

Location

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

Hartford, Connecticut, 06105, United States

Location

Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, 19958, United States

Location

CCOP - Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Memorial Cancer Institute at Memorial Regional Hospital

Hollywood, Florida, 33021, United States

Location

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Ella Milbank Foshay Cancer Center at Jupiter Medical Center

Jupiter, Florida, 33458, United States

Location

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, 32803-1273, United States

Location

John B Amos Cancer Center

Columbus, Georgia, 31904, United States

Location

Cancer Research Center of Hawaii